Intra-operative confocal imaging-guided Mohs surgery

描述(由申请人提供)： 该方案的目的是开发和临床测试一种基于共聚焦反射显微镜的实时光学成像模式，并使用醋酸和交叉偏振增强核与真皮的对比，以在术中检查基底细胞癌，以指导莫氏显微外科手术。基底细胞癌(BCC)是增长最快的癌症之一(美国每年新增120万例)；由于它们最常发生在老年人和高危解剖部位(眼睛、口腔、鼻子、耳朵附近或周围)，精确的显微手术是必要的，对周围正常组织的损害最小。Mohs手术耗时(一到几个小时)且繁琐，因为必须进行几次(2-20)切除，并仔细准备和检查每一次的冰冻组织切片。实时共聚焦反射成像可以通过术中直接检查患者的癌巢和癌与正常组织边缘，从而显著提高Mohs手术的效率；这将减少切除的次数，避免冰冻的组织学检查。病人和外科医生在手术室的每一次手术都将节省几个小时。虽然建议用于基底细胞癌的Mohs手术，但这种术中实时成像方式实际上可能在各种其他显微外科环境中被证明是有用的。这项研究将由东北大学(波士顿)和纪念斯隆-凯特琳癌症中心(纽约)合作进行。该项目将分两个阶段实施：(1)使用Mohs手术新鲜切除的皮肤标本的体外研究，以(A)设计一种模仿Mohs手术医生冰冻组织学检查的共聚焦显微镜：在大视野中快速低分辨率检查BCC巢，然后在小视野中高分辨率检查核形态，并开发(B)使用局部醋酸(导致染色质凝结，增加来自细胞核的光后向散射)和光学交叉偏振(抑制来自周围正常真皮的光后向散射)的最佳对比增强方法，(C)使用局部氯化铝或电灼术的最佳止血方法，(D)通过图像与组织学的详细关联来理解图像；(2)术中研究，包括(A)设计专门的共聚焦关节望远镜，以便(B)术中对患者的基底细胞癌进行成像，评估最佳的对比度增强和止血方法，将共聚焦图像与组织学相关联，并定量确定诊断/筛查的准确性。总体目标是开发一种光学(共焦)术中成像仪器，用于MoHS和其他模式的显微外科手术。

DESCRIPTION (provided by applicant): The goal of this proposal is to develop and clinically test a real-time optical imaging modality based on confocal reflectance microscopy, with enhancement of nuclear-to-dermal contrast using acetic acid and crossed polarization, to intra-operatively examine basal cell cancers to guide Mohs micrographic surgery. Basal cell cancers (BCCs) are among the fastest growing cancers (>1.2 million new USA cases/year); because they occur most frequently on older people and in high risk anatomical sites (near or on the eyes, mouth, nose, ears), precise microsurgery is necessary with minimum damage to the surrounding normal tissue. Mohs surgery is time-consuming (one to several hours) and tedious because several (2-20) excisions must be made, and frozen histology sections carefully prepared and examined for each. Realtime confocal reflectance imaging may make Mohs surgery significantly more efficient by enabling direct intraoperative examination for cancer nests and cancer-to-normal tissue margins on the patient; this will reduce the number of excisions and avoid frozen histology. Both the patient and surgeon will save several hours per procedure in the operating room. Although proposed for Mohs surgery of BCCs, this real-time intra-operative imaging modality may, in fact, prove useful in a variety of other microsurgical settings. The research will be a collaboration between Northeastern University (Boston) and Memorial Sloan-Kettering Cancer Center (New York). This project will be implemented in two phases: (1) an ex vivo study using freshly excised skin specimens from Mohs surgeries, to (a) design a confocal microscope that mimics the Mohs surgeon's examination of frozen histology: rapid low-resolution examination of BCC nests in wide fields-of-view followed by high-resolution inspection of nuclear morphology in small fields-of-view, and develop (b) optimum contrast enhancement methods using topical acetic acid (induces condensation of chromatin that increases light backscatter from nuclei) and optical crossed polarization (suppresses light backscatter from the surrounding normal dermis), (c) optimum hemostasis methods using either topical aluminum chloride or electrocautery, (d) image understanding by detailed correlation of images to histology; and (2) an intraoperative study, involving (a) design of a specialized confocal articulated telescope, to enable (b) imaging of BCCs on patients during surgery, to evaluate the optimum contrast enhancement and hemostasis methods, correlate confocal images to histology and quantitatively determine diagnostic/screening accuracy. The overall goal is to develop an optical (confocal) intra-operative imaging instrument for Mohs and other modes of microsurgery.